page_title: RNase MRP
section_title: Mechanism and mutation effects
hierarchical_section_title: RNase MRP / Mechanism and mutation effects
caption_attribution_description: English: RNA MRP Regulation of Cell Cycle through Clb mRNA levels
context_page_description: RNase MRP is an enzymatically active ribonucleoprotein with two distinct roles in eukaryotes. RNAse MRP stands for RNAse for mitochondrial RNA processing. In mitochondria it plays a direct role in the initiation of mitochondrial DNA replication. In the nucleus it is involved in precursor rRNA processing, where it cleaves the internal transcribed spacer 1 between 18S and 5.8S rRNAs. Despite distinct functions, RNase MRP has been shown to be evolutionarily related to RNase P. Like eukaryotic RNase P, RNase MRP is not catalytically active without associated protein subunits.
  Mutations in the RNA component of RNase MRP cause cartilage–hair hypoplasia, a pleiotropic human disease. Responsible for this disease is a mutation in the RNase MRP RNA gene, a non-coding RNA gene. RMRP was the first non-coding nuclear RNA gene found to cause disease.
context_section_description: RNAase MRP and its role in pre-rRNA processing has been previously studied in Yeast cells. RNase MRP has been shown to cleave an internal transcribed spacer, specifically ITS1 at the specific site A3 of the rRNA precursor, leading, after additional trimming, to the formation of the mature 5′-end of 5.8S rRNA.
  Recent data that has been gathered using several temperature-sensitive RNase MRP mutants that showed that inactivation of RNase MRP leading to severe reduction of the abundance of all early intermediates in the typical rRNA processing pathway. However, the transcription of the rRNA precursor is not affected, thus suggesting that RNase MRP plays a key role in the processing of rRNA beyond the cleavage of the A3 site in ITS1.
  Further research in Yeast cell RNase MRP has shown a potential role in the regulation of the cell cycle. RNase MRP mutations led to missegregation of plasmids and caused cell cycle delay at the end of mitosis, followed by a buildup of cyclin B2 (CLB2) protein (resulting from increased CLB2 mRNA concentration that codes for the CLB2 protein). RNase MRP also demonstrated cleavage ability of the 5′-UTR of CLB2 mRNA that allows for rapid 5′-to-3′ degradation by XRN1, an exoribonuclease enzyme.
caption: Diagram of RNase MRP role in cell cycle control. Rnase MRP degrades CLB2 mRNA. CLB2 mRNA is processed to create an uncapped RNA transcript. This transcript is then degraded by Xrn1 5'-3' exoribonuclease. Defective RNase MRP results in increased CLB2 mRNA and protein. Maintained CLB2 protein levels allows Cdc28 (a cyclin-dependent kinase) to remain active and inhibit the end of mitosis.
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